Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Plantas medicinais em feiras e mercados públicos do Distrito Florestal Sustentável da BR-163, estado do Pará, Brasil Medicinal plants at fairs and public markets of the Sustainable Forest District of BR-163, Pará state, Brazil

As plantas medicinais constituem um grupo de produtos florestais não-madeireiros apontado como de grande potencial no Distrito Florestal Sustentável da BR-163. Visando compreender a cadeia produtiva de plantas medicinais oriundas do extrativismo, comercializadas em entrepostos, feiras e mercados públicos de municípios desta área, foram realizadas entrevistas semi-estruturadas com 20 vendedores de plantas medicinais. Foi estimada a riqueza de espécies a partir do estimador Bootstrap e analisada a similaridade entre os municípios estudados, através do Índice de Sørensen. Identificaram-se 46 etnoespécies de plantas medicinais, pertencentes a 42 gêneros e 21 famílias, sendo Fabaceae, Anacardiaceae e Bignoniaceae as famílias mais representativas. A riqueza esperada foi de 50 etnoespécies, sendo que coletas adicionais acrescentariam pelo menos quatro itens à lista geral de riqueza. Com relação à similaridade, Santarém, Itaituba e Altamira compartilham um maior número de espécies, sendo que Santarém mostra-se como centro diversificado de produtos medicinais, com maior número de ocorrências exclusivas (14). As feiras e mercados públicos, por serem um elo importante desse sistema de distribuição, devem ser incluídos nas ações governamentais sobre políticas públicas para a saúde.<br>Medicinal plants are non-timber forest products with great potential in the Sustainable Forest District of BR-163. In order to understand the productive chain from extractive medicinal plants marketed at emporiums, fairs and public markets of districts of this area, semi-structured interviews with 20 vendors of medicinal plants were carried out. Species richness was estimated by Bootstrap and similarity among the districts studied was analyzed by Sørensen's Index. 46 medicinal plants belonging to 42 genera and 21 botanical families were identified. Fabaceae, Anacardiaceae and Bignoniaceae were the most representative botanical families. The expected richness for the sample was 50 species and additional collecting would increase by at least four items the general list of richness. Santarém, Itaituba and Altamira share a larger number of species and the first is shown to be a diversified center of medicinal products, presenting the largest number of exclusive occurrences (14). The fairs and public markets are an important link of this distribution system, and should be included in government actions concerning public policies for health